Are there stem cell therapies available for Duchenne’s muscular dystrophy?

To our knowledge, no stem cell therapy has received Health Canada or U.S. Food and Drug Administration for treatment of Duchenne’s muscular dystrophy at this time. Patients who are researching their options may come across companies with Web sites or materials that say otherwise and offer fee-based stem cell treatments for curing this disease. Many of these claims are not supported by sound scientific evidence and patients considering these therapies are encouraged to review some of the links below before making crucial decisions about their treatment plan.

How close are we? What do we know about Duchenne’s muscular dystrophy?

Duchenne’s muscular dystrophy (Duchenne’s) is the most common and severe type of neuromuscular disease. It leads to progressive muscle weakness and wasting.

Duchenne’s is an inherited disease caused by a mutation in the dystrophin gene.

Dystrohin is the protein that stabilizes muscle cells and keeps them intact during the normal wear and tear of the day.

Without dystrophin, muscle cells cannot regenerate properly and they become progressively more inflamed and waste away over time.

Duchenne’s is an X-linked disease (passed on by the mother) and it affects one in every 3,500 boys who typically succumb to paralysis and death in their twenties from respiratory or cardiac complications.

There is no cure for Duchenne’s muscular dystrophy. Treatments that control symptoms and aim to improve quality of life include steroids, physiotherapy, braces and wheelchairs, spinal surgery and breathing aids.

How can stem cells play a part?

Because Duchenne’s muscular dystrophy is caused by the deficiency of one gene product – the dystrophin protein – there is hope that stem cells will someday provide a viable treatment option. Scientists have identified different muscle forming stem cells in skeletal muscle, bone marrow, blood, fat, and other tissues. Currently, the two main applications of stem cells for treating Duchenne’s are as cells to regenerate damaged muscle or as vehicles to deliver gene therapies that replace or repair the defective gene.

Are there lots of groups working on developing a stem cell therapy?

There are many research teams around the globe working to develop stem cell therapies for Duchenne’s muscular dystrophy. Their common goals are to identify which stem cells are best suited for the job, which signals will be able to coax them into becoming muscle cells, and the large scale lab methods required for ramping up the production of the required cells.

Understanding the role played by satellite cells is one of the important research contributions to date. Satellite cells were discovered 50 years ago, but it has taken many years to decipher that they are the cells responsible for all the growth, maintenance and repair of skeletal muscles. In response to injury, satellite cells either turn into muscle cells that fuse together to build or repair muscle fibres, or divide and remain dormant in muscle tissue waiting to be called on to regenerate muscle at a later time.

Stem cell research for muscular dystrophy is proceeding at a steady pace but only a handful of results have been translated into early Phase 1 clinical trials. Since 1992, the majority of these have been very small trials, testing the safety and effectiveness of using muscle precursors from the bone marrow to treat boys with Duchenne’s. In the past five years, a major focus has been working out the important variables that will push research forward and provide new and safe opportunities for testing stem cells in clinical trials for this disease.

What research is underway?

The main types of stem cells being considered for Duchenne’s muscular dystrophy are adult stem cells in skeletal muscle and bone marrow, and pluripotent stem cells that are either man-made or from the embryo. Research using pluripotent stem cells is still at the preclinical stage but research using adult stem cells has progressed to a few small Phase 1 trials. Many challenges remain.

Researchers are still trying to understand which stem cells are ideal for treating Duchenne’s and have identified certain qualities that make some stem cells better candidates than others. Ideally, the best choice would be a stem cell that can be grown, expanded, turned into muscle-forming cells in a dish, and delivered system-wide to target damaged skeletal muscle all over the body. Once the stem cells or muscle-forming cells are transplanted, they must be able to survive, grow and migrate to the site of damaged skeletal muscle – and if possible do all this without provoking transplant rejection in the recipient. Lastly, the best stem cell candidate should also be able to make the dystrophin protein as this will maximize muscle function. In the search for the ideal stem cell to treat Duchenne’s, researchers have found that muscle stem cells do a better job of rebuilding muscle when they are embedded in a matrix that resembles the normal architectural support that cells have in the body. For example, satellite cells embedded in biodegradable 3D scaffolds are better able to form normal skeletal muscle in a dish. The ability to expand skeletal muscle in a dish is important for future regenerative therapies and the 3D scaffold approach may become a useful tool for achieving this goal.

The road to finding a stem cell therapy for Duchenne’s is paved with many challenges that will take time to overcome, but the convergence of information generated from labs around the globe is helping to speed the transition from basic research to the clinic. The results are promising and in time may point to a viable stem cell therapy that can repair and regenerate lost muscle and provide an enduring therapy for boys with Duchenne’s muscular dystrohpy.

Current research using skeletal muscle stem cells

There are a number of different skeletal muscle stem cells (called precursors) that are being explored for their ability to treat Duchenne’s, but many challenges hamper their development as a regenerative therapy. In 1991, very small clinical trials showed that myoblasts, a type of muscle stem cell precursor, could produce dystrophin in boys with Duchenne’s. Although this was the proof-of-principle that a stem cell therapy could work, studies since have not shown the hoped for improvements in muscle strength. Pre-clinical research using satellite cells extracted from muscle biopsies has shown some promise as these cells can be injected into animal muscle where they efficiently fuse with muscle fibres, make dystrophin and even more satellite cells. But only small numbers of satellite cells can be extracted from muscle biopsies so researchers are looking for alternate sources, and better ways to expand the cells in the laboratory. Mesangioblasts come from a population of stem cells associated with blood vessels in skeletal muscle. Animal studies have corroborated that mesangioblasts injected into the blood can partially restore dystrophin levels in the target muscles and possibly buttress the stem cell pool of satellite cells. Results from a Phase 1 clinical trial testing the safety and effectiveness of these muscle stem cells are soon to be published.

Current research using bone marrow stem cells

Bone marrow stem cells can also make muscle-forming cells, which are capable of finding areas of muscle degeneration and contributing to muscle repair in mice. Two of the main advantages of bone marrow stem cells are that they are very easily harvested and systemic delivery is routinely possible. However, the levels of contribution to muscle are extremely low, making the regenerative approach not a viable option at this time. Recently, however, scientists have co-opted bone marrow stem cells to deliver a gene therapy called ‘MAGIC-Factor-1’ that can repair damaged muscle in mice. Phase 1 clinical trials using bone marrow stem cells to deliver MAGIC- Factor-1 in patients with Duchenne’s have so far shown no adverse events.

Current research using pluripotent stem cells

In nature, the master stem cell is the embryonic stem cell because it can make an entire human being. Researchers have recently found a way to turn back the clock on adult cells and reprogram them to act like embryonic stem cells. These man-made stem cells are called induced pluripotent stem cells or iPS cells (‘pluripotent’ from the Latin words ‘very many’ and ‘having power’) and they can be made from skin or other tissue cells.

Although pluripotent stem cells are powerfully regenerative and capable of making the necessary cells to repair injured muscle, concerns about the ethics of their use and/or the potential of tumour formation has made their application as therapies proceed with caution. Preclinical studies have shown that it is possible to stimulate embryonic stem cells to make skeletal muscle precursors, which can contribute to muscle formation without forming tumours when transplanted into mice. In 2010, researchers collaborating internationally were able to correct the dystrophin gene defect in skin cells from a patient with Duchenne’s muscular dystrophy and turn the cells into iPS cells. If this process could be perfected, it might someday be used for generating patient-specific transplants that could restore dystrophin levels in individuals with Duchenne’s.

Further reading on Duchenne’s muscular dystrophy

Readers may wish to peruse the recommended sites and articles below for more information about Duchenne’s muscular dystrophy and the possible applications of stem cells to treat this disease.

Research is a dynamic activity that creates new knowledge. It provides a forum for generating observations and testing why they occur. Because people and their diseases are so diverse, clinical trials are the only way possible to test whether new ideas about how to diagnose or treat human disease will work. The process of taking research from the laboratory bench to the patient's bedside is a lengthy one and demands not only vision but also years of teamwork and dedication on the part of scientists, physicians and patients.

This information summarizes current research ideas on how stem cells could be used to achieve new treatments. The content presented is by no means exhaustive and readers may wish to peruse additional Web resources or speak with their physicians for more information.

The Canadian Stem Cell Foundation, in partnership with the Stem Cell Network, would like to acknowledge the contribution of the members of the Stem Cells and Disease Editorial Advisory Panel.